Amyotrophic lateral sclerosis (ALS, sometimes called Lou Gehrig's Disease) is a progressive, usually fatal, neurodegenerative disease caused by the degeneration of motor neurons, the nerve cells in the central nervous system that control voluntary muscle movement. As one of the motor neuron diseases, the disorder causes muscle weakness and atrophy throughout the body as both the upper and lower motor neurons degenerate and die, ceasing to send messages to muscles. Unable to function, the muscles gradually weaken, develop fasciculations (twitches) because of denervation, and eventually atrophy due to denervation. The patient may ultimately lose their ability to initiate and control all voluntary movement except of the eyes.
Cognitive function is generally spared except in certain situations such as when ALS is associated with frontotemporal dementia. However there are reports of more subtle cognitive changes of the frontotemporal type in many patients when detailed neuropsychological testing is employed. Sensory nerves and the autonomic nervous system, which controls functions like sweating, generally remain functional.
ALS is one of the most common neuromuscular diseases worldwide, and people of all races and ethnic backgrounds are affected. Between 1 to 2 people per 100,000 develop ALS each year. ALS most commonly strikes people between 40 and 60 years of age, but younger and older people can also develop the disease. Men are affected slightly more often than women. ALS is genetically heterogeneous, and the known genes explain only 5% of the disease. Ninety percent of ALS cases are sporadic (SALS) and 10% are familial (FALS) with dominant inheritance most common.
The onset of ALS may be so subtle that the symptoms are frequently overlooked. The earliest symptoms may include twitching, cramping, or stiffness of muscles; muscle weakness affecting an arm or a leg; and/or slurred and nasal speech. Regardless of the part of the body first affected by the disease, muscle weakness and atrophy spread to other parts of the body as the disease progresses. Patients experience increasing difficulty moving, swallowing (dysphagia), and speaking or forming words (dysarthria). Eventually patients will not be able to stand or walk, get in or out of bed on their own, or use their hands and arms. Because the disease usually does not affect cognitive abilities, patients are aware of their progressive loss of function and may become anxious and depressed. A small percentage of patients go on to develop frontotemporal dementia characterized by profound personality changes; this is more common amongst those with a family history of dementia. A larger proportion of patients experience mild problems with word-generation, attention, or decision-making. Cognitive function may be affected as part of the disease process or could be related to poor breathing at night (nocturnal hypoventilation).
No cure has yet been found for ALS. However, the Food and Drug Administration (FDA) has approved the first drug treatment for the disease: Riluzole (Rilutek). Riluzole is believed to reduce damage to motor neurons by decreasing the release of glutamate. Clinical trials with ALS patients showed that riluzole prolongs survival by several months, and may have a greater survival benefit for those with a bulbar onset. The drug also extends the time before a patient needs ventilation support. Riluzole does not reverse the damage already done to motor neurons, and patients taking the drug must be monitored for liver damage and other possible side effects.
Clearly there is a great need for characterization of the poorly understood molecular basis of ALS as well as for improved diagnostics and treatments for ALS.